I. Field of the Invention
The present invention relates to a method for producing human lymphocytes producing antibodies specific to desired antigens and a method for producing monoclonal antibodies, as well as to monoclonal antibodies produced thereby.
II. Description of the Related Art
Antibodies are conventionally administered to humans for the purpose of treating or diagnosing various diseases. The conventionally used antibodies are prepared mainly from animals such as mice. However, when an antibody obtained from an animal is administered to a human for treating a disease, an anti-antibody is produced, so that the half life of the administered antibody is short and sufficient effect is not obtained by repeatedly administering the antibody. Further, there are antigens such as HD antigen which cannot be prepared from mice. Although this problem may be overcome by directly recovering lymphocytes from humans, since the human lymphocytes producing an antibody specific to the desired antigen cannot be recovered systematically, this approach is not industrially viable. Further, since it is not generally permitted to immunize human with a desired antigen from an ethical view point, it is difficult to obtain a lymphocyte producing the desired antibody. Further, even in cases where the desired antigen can be administered to humans, it is impossible to repeatedly immunize the human for a long time, so that it is difficult to induce a sufficient immune response.
To overcome the above-mentioned problem, the transformation method employing Epstein-Barr virus (D. Kozbor et al., Methods in Enzymology, 121 140 (1986)) and the in vitro sensitization method (C. A. K. Borrebaeck et al., J. of Immunology, 136, 3710 (1986)) have been proposed. However, most of the antibodies produced by these methods are IgMs. IgMs are difficult to purify and their stabilities are not high. Further, with the in vitro sensitization method, since lymphocytes are cultured with an antigen, the time period in which the lymphocytes can be sensitized is short, so that it is difficult to induce sufficient antibody production. Thus, a method for producing a human monoclonal antibody, especially a human IgG antibody, which is specific to a desired antigen, is desired.